Journal of Diabetes and Endocrinology Vol. 3(5), pp. 57-69, November 2012 Available online at http://www.academicjournals.org/JDE DOI: 10.5897/JDE11.017 ISSN 2141-2685 ©2012 Academic Journals Review Hypothyroidism in adults: A review and recent advances in management F. Bello* and A. G. Bakari Department of Medicine, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. Accepted 3 February, 2012 Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid hormone or, more rarely, from their impaired activity at tissue level. In its clinically overt form, hypothyroidism is a relatively common condition, with an approximate prevalence of 2% in adult women and 0.2% in adult men. Deficiency of the hormone has a wide range of effects, because all metabolically active cells require thyroid hormone. The clinical features of hypothyroidism are dependent on the patient's age, the presence of other disease, and the rate at which hypothyroidism develops. Early detection and proper management is very important. Under treatment leads to disease progression with gradual worsening of symptoms and further metabolic derangements. Fortunately, in most patients older than 3 years, the signs and symptoms of hypothyroidism are reversed with thyroid hormone treatment. A constant reminder on progress in management of the disease is needed. Thus, the aim of this review is to bring to notice the recent advances in the diagnosis and management of hypothyroidism and to highlight the risks involved in the global movement from consuming organic animals (as the world moves towards inorganic foods, which inhibits thyroid hormones). Key words: Hypothyroidism, thyroid gland, deficiency. INTRODUCTION Hypothyroidism is a common endocrine disorder autoimmune thyroid disease (Hashimoto thyroiditis). It resulting from deficiency of thyroid hormone or, more may begin in utero or later in life. Hypothyroidism is rarely, from their impaired activity at tissue level. Pre- characterized by a generalized reduction in metabolic valence is 1.9% in women, and it increases with age. It function that most often manifests as a slowing of may be a primary process in which the thyroid gland physical and mental activity. Subclinical hypothyroidism, produces insufficient amounts of thyroid hormone (e.g. referred to as mild hypothyroidism, is defined as normal autoimmune thyroiditis, previous radio-iodine or surgical serum free thyroxine (T4) levels with slightly high serum treatment of hyperthyroidism), but can also be se- TSH concentration. The clinical features of hypo- condary, that is, lack of thyroid hormone secretion due to thyroidism are dependent on the patient's age, the inadequate secretion of either thyrotropin (that is, thyroid- presence of other disease, and the rate at which hypo- stimulating hormone [TSH]) from the pituitary gland or thyroidism develops. thyrotropin-releasing hormone (TRH) from the hypo- Recently, in a 12-year longitudinal study, Stuckey et al. thalamus (secondary or tertiary hypothyroidism). The (2010) reported the long-term risk of hypothyroidism in patient's presentation may vary from asymptomatic to, women who previously had postpartum thyroid dys- rarely, coma with multisystem organ failure (myxedema function (PPTD). The study involved 409 women, 71 of coma). The most common cause in the United States is whom had previously been diagnosed with PPTD. At 12- year follow-up, 27 women in the PPTD group and 14 women in the non-PPTD group (38 and 4%, respectively) were found to have hypothyroidism. The authors conclu- *Corresponding author. E-mail: [email protected]. Tel: ded that within the PPTD group, women who had been +2348034525925. diagnosed with postpartum hypothyroidism were among 58 J. Diabetes Endocrinol. those at a particularly high long-term risk for effects, because all metabolically active cells require hypothyroidism (OR = 9.7). thyroid hormone. Systemic effects are due to either de- rangements in metabolic processes or direct effects by myxedematous infiltration (that is, accumulation of glu- THYROID PHYSIOLOGY cosaminoglycans in the tissues). Subsequently, the effects of thyroid hormone Thyroid hormones are the only iodine-containing deficiency on growth and development, on intermediary substances of physiologic significance in vertebrates. metabolism, on central nervous system development and Thyroid cells actively extract and concentrate iodide from function, and on cardiovascular, skeletal, gastrointestinal, plasma. T4, a prohormone, is converted to triiodo- and reproductive system activity have been charac- thyronine (T3), the active form of thyroid hormone, in the terized. They are briefly summarized subsequently. peripheral tissues by 5’-deiodination. Early in the disease process, compensatory mechanisms maintain T3 levels. Normal thyroid produces all of the circulating T4 and Growth and development about 20% of the circulating T3 (Surks et al., 2004). Most of the biologic activity of thyroid hormones is due to the Thyroid hormone exerts profound effects on growth and cellular effects of T3, which has a greater affinity for the development during the first 2 decades of life. Thyroid thyroid hormone receptor and is approximately 4 to 10 hormone deficiency adversely affects the development of times more potent than T4 (Surks et al., 1973; Sawin et the central nervous system (Langsteger et al., 1994; al., 1977). 80% of serum T3 is derived from the Rodriguez-Pena, 1999; Bernal and Nunez, 1995), deiodination of T4 in tissues such as the liver and kidney. auditory system (Dussault and Ruel, 1987), and skeletal Once T4 and T3 are released into the circulation, they system (Sohmer and Freeman, 1996). Hypothyroidism are bound by thyroxine-binding globulin (TBG), also delays dental development and eruption (Williams et transthyretin (thyroxine-binding prealbumin), and albu- al., 1998). min. Thyroxine-binding globulin has the highest affinity The combination of maternal and fetal hypo- for T4 and T3 and the lowest capacity, whereas albumin thyroxinemia produced by iodine deficiency is associated has the lowest affinity and the highest capacity. Only the with irreversible fetal central nervous system damage free (unbound) fraction of T4 and T3 is able to bind to (Pirinen, 1995). Preliminary evidence suggests that low specific thyroid hormone receptors in peripheral tissues maternal free thyroxine concentration may impair neuro- and possesses biologic activity. Normally, approximately development in the healthy fetus (Fisher, 1997). A recent 0.03% of T4 and 0.5% of T3 is free (The National study indicates that maternal hypothyroxinemia produces Academy of Clinical Biochemistry, 1996; Oppenheimer et alterations in the activity of neurotransmitter metabolic al., 1972) (Figure 1). enzymes that have putative neurotropic functions in brain Changes in the binding capacity of thyroid hormone development (James et al., 1999). transport proteins may significantly affect the measure- Although, the function of the fetal hypothalamic- ment of total thyroid hormone concentration and thereby pituitary axis develops autonomously of the mother, it is complicate the diagnosis of hypothyroidism. The dependent on maternal supply of iodine derived mostly accurate diagnosis of thyroid disease is more difficult in from placental deiodination of T4. The placenta is imper- patients with multiple abnormalities in thyroid hormone- meable to TSH and permeable to TRH. Under normal cir- binding proteins (Robbins, 1992). Table 1 lists factors cumstances, neither T3 nor T4 freely crosses the placenta and conditions that alter thyroid hormone binding to a large extent. However, it appears that the maternal proteins and may make the diagnosis of hypothyroidism contribution of T4 increases in cases of congenital difficult. hypothyroidism. In a study of infants who were unable to synthesize T4, cord serum levels of T4 were 35 to 70 nmol/L (Evans et al., 1999). This suggests an increased Pathophysiology transport of T4 from the mother to the fetus. Thus, trans- placental movement of maternal T4 may provide a partial Localized disease of the thyroid gland that results in explanation for the relatively normal clinical appearance decreased thyroid hormone production is the most at birth of most infants with congenital hypothyroidism. common cause of hypothyroidism. Under normal circum- Thyroid replacement initiated shortly after birth mini- stances, the thyroid releases 100 to 125 nmol of T4 daily mizes the risk of permanent brain damage, because two and only small amounts of T3. Decreased production of thirds of postnatal brain growth and differentiation occurs T4 causes an increase in the secretion of TSH by the during the first 2 years of life. Thyroid hormone deficiency pituitary gland. TSH stimulates hypertrophy and hyper- that develops after 3 years of age is not associated with plasia of the thyroid gland and thyroid T4-5'- deiodinase mental impairment, but is associated with delayed soma- activity. This in turn causes the thyroid to release more tic and linear bone growth and delayed eruption of per- T3. Deficiency of the hormone has a wide range of manent teeth. Early detection and treatment of The iodide cycle. Ingested iodide is trapped in the thyroid, oxidized, and bound to tyrosine to form iodotyrosines in thyroglobulin (TG); coupling of iodotyrosyl residues forms T4 and T3. HormoneBello secreted and Bakari by 59 the gland is transported in serum. Some T is deiodinated to T . The hormone exerts its metabolic effect 4 3 on the